Knee osteoarthritis (OA) is associated with substantial pain and disability. The course of knee OA is variable gaps in knowledge of determinants of the natural history of knee OA relate in part to the complexity of investigation. A widely accepted paradigm views knee OA severity as a result of local neuromechanical factors, acting against a background of susceptibility determining systemic factors (e.g. age related, genetic). The neuromechanical status of the knee is theoretically determined by both aspects of structure (especially alignment and laxity) and joint protecting neuromuscular reflexes (requiring joint position sense and muscle contraction). Impairments in these factors result in increased, suboptimally distributed load transmitted to the articular surface, and we suspect are associated with accelerated disease progression. We propose here to test the hypothesis that neuromechanical factors, malalinment, increased laxity, proprioception deficit, and muscle weakness are associated with more rapid progression of knee OA. Our specific aims are: 1) to measure in 300 symptomatic, tibiofemoral knee OA patients with definite osteophytes, at baseline, 18 months and 36 months, each of the neuromechanical variables noted; 2) to assess change in functional status, the primary outcome, using the Western Ontario and McMaster University OA Index Physical Function scale, and radiographic status by measuring joint space width with a magnifying lens fitted with a graticule, from the standing semi-flexed radiograph; and 3) to analyze the contribution of each of the neuromechanical factors to outcome, while controlling for potentially confounding variables, using analytic methods that allow data from both knees to be considered. We believe that the results of this study will delineate the specific events that caus progression of knee OA, allow correct interpretation of therapeutic trial results, and facilitate early, cost-effective intervention in neuromechanical subsets at particular risk for decline.